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Restrictive vs Liberal Transfusion Strategy in Patients with Myocardial Infarction and Anemia

In studies involving over 21,433 critical care patients, randomized trials comparing restrictive and liberal transfusion strategies revealed a 50% reduction in blood utilization with no significant impact on morbidity or mortality rates. Current transfusion guidelines recommend transfusion for hemoglobin level less than 7 g/dL in general critical care patients and underscore the need for more extensive clinical trials in patients who have experienced myocardial infarction and acute coronary syndrome.

The rationale for blood transfusion in myocardial injury involves enhancing oxygen supply to the cardiac tissues, potentially diminishing the likelihood of subsequent myocardial infarction or mortality. However, there are potential adverse effects to consider, such as cardiac failure due to volume overload, increased risk of infection due to immunosuppressive effects of transfusion, thrombotic events owing to elevated blood viscosity, and inflammatory responses.

A restrictive transfusion approach was compared to a liberal one in three small, randomized trials with 820 patients who had myocardial infarction. The results were not consistent [1-3].


The first pilot study compared transfusion strategies for anemic patients with acute myocardial infarction (AMI), 45 patients were randomized to either a liberal strategy (maintaining hematocrit 30-33%) or a conservative strategy (maintaining hematocrit 24-27%). The liberal strategy was associated with worse clinical outcomes, including higher rates of in-hospital death, recurrent MI, or worsening heart failure (38% vs 13%). These findings highlighted the potential risks of liberal transfusion in this patient group and suggest the need for a larger trial to further investigate these outcomes [1].



Another pilot trial with 110 patients having acute coronary syndrome or stable angina and low hemoglobin, a liberal transfusion strategy (raising hemoglobin ≥10 g/dL) was compared with a restrictive strategy (transfusion for hemoglobin <8 g/dL or anemia symptoms). The liberal strategy led to more transfusions and was associated with fewer major cardiac events (10.9% vs. 25.5%) and lower 30-day mortality (1.8% vs. 13.0%) compared to the restrictive strategy. These findings indicate a potential benefit of the liberal strategy and the necessity for a larger, definitive trial [2].

The largest of these studies involved 668 patients with acute myocardial infarction and anemia (the REALITY Trial). A restrictive transfusion strategy (triggered at a hemoglobin level ≤8 g/dL) was compared to a liberal strategy (triggered at ≤10 g/dL). The main outcome measured was major adverse cardiovascular events (MACE: a composite of all-cause death, stroke, recurrent myocardial infarction, or emergency revascularization prompted by ischemia) within 30 days. The study found that the restrictive strategy was noninferior to the liberal strategy in terms of MACE rates, but there was a potential for clinically significant harm, as indicated by the confidence interval [3].


In the other clinical situations involving patients after cardiac surgery without acute myocardial infarction, a restrictive strategy decreased blood use by 50% without adversely affecting clinical outcomes [4-5].

The MINT Trial
The MINT Trial

The MINT trial, a phase 3 interventional study, compared restrictive and liberal transfusion strategies in patients with myocardial infarction and hemoglobin levels below 10 g/dL. The restrictive strategy involved transfusions when hemoglobin fell below 7 or 8 g/dL, while the liberal strategy involved transfusions when hemoglobin was less than 10 g/dL. The primary outcome was a combination of myocardial infarction or death at 30 days [6].


Involving 3504 patients, the trial found that those in the restrictive group received fewer transfusions (mean 0.7 units) than those in the liberal group (mean 2.5 units). The restrictive group also maintained lower hemoglobin levels for the first three days post-randomization. The occurrence of primary outcome events was slightly higher in the restrictive group (16.9%) compared to the liberal group (14.5%). Specifically, death occurred in 9.9% of patients in the restrictive group and 8.3% in the liberal group, while myocardial infarction occurred in 8.5% and 7.2%, respectively.


The conclusion was that a liberal transfusion strategy did not significantly reduce the risk of recurrent myocardial infarction or death at 30 days in patients with acute myocardial infarction and anemia, but potential harms of a restrictive strategy could not be ruled out.

Based on the previous studies, what is your transfusion threshold for patients with myocardial infarction and anemia?

  • 0%Hg <7 mg/dL

  • 0%Hg <8 mg/dL

  • 0%Hg <9 mg/dL

  • 0%Hg <10 mg/dL



REFRENCES
  1. Cooper HA, Rao SV, Greenberg MD, et al. Conservative versus liberal red cell transfusion in acute myocardial infarction (the CRIT randomized pilot study). Am J Cardiol 2011;108:1108-1111.

  2. Carson JL, Brooks MM, Abbott JD, et al. Liberal versus restrictive transfusion thresholds for patients with symptomatic coronary artery disease. Am Heart J 2013;165(6):964.e1-971.e1.

  3. Ducrocq G, Gonzalez-Juanatey JR, Puymirat E, et al. Effect of a restrictive vs liberal blood transfusion strategy on major cardiovascular events among patients with acute myocardial infarction and anemia: the REALITY randomized clinical trial. JAMA 2021;325:552-560.

  4. Murphy GJ, Pike K, Rogers CA, et al. Liberal or restrictive transfusion after cardiac surgery. N Engl J Med 2015;372:997-1008.

  5. Mazer CD, Whitlock RP, Fergusson DA, et al. Restrictive or liberal red-cell transfusion for cardiac surgery. N Engl J Med 2017;377:2133-2144.

  6. Carson JL, Brooks MM, Hébert PC, Goodman SG, Bertolet M, Glynn SA, Chaitman BR, Simon T, Lopes RD, Goldsweig AM, DeFilippis AP, Abbott JD, Potter BJ, Carrier FM, Rao SV, Cooper HA, Ghafghazi S, Fergusson DA, Kostis WJ, Noveck H, Kim S, Tessalee M, Ducrocq G, Gabriel Melo de Barros E Silva P, Triulzi DJ, Alsweiler C, Menegus MA, Neary JD, Uhl L, Strom JB, Fordyce CB, Ferrari E, Silvain J, Wood FO, Daneault B, Polonsky TS, Senaratne M, Puymirat E, Bouleti C, Lattuca B, White HD, Kelsey SF, Steg PG, Alexander JH; MINT Investigators. Restrictive or Liberal Transfusion Strategy in Myocardial Infarction and Anemia. N Engl J Med. 2023 Nov 11. doi: 10.1056/NEJMoa2307983. Epub ahead of print. PMID: 37952133.

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2 Comments


Ibrahim Ameen
Ibrahim Ameen
Nov 15, 2023

Amazing summery as usual, Dr.Mazen

Thanks for keeping us informed

The corporation between the ICU and CCU is well known and wel established in most centres

And thess studies have looked at MI (STEMI & NSTEMI) pt, not unstable angina. And it has to be an acute event, not a hx of MI

Which our ICU pt could develop at any moment

Even though the statistical significance has not been reached. We could see some deference. The sample size was an adequate large sample.

What was the target deference in order to show significant statistical differences in this model?

Also, the second question is: How long should we maintain this target?

And I can't put my finger on the bias…

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Mazen Kherallah
Mazen Kherallah
Nov 15, 2023
Replying to

Thank you for your comment, the anticipated difference was 20% difference between the two groups and the observed was 15%. The trial included patients with STEMI and NSTEMI.

The fact that randomization was not masked, may have affected their results and introduced some bias as this factor may have influenced the use of revascularization, or other interventions, or the classification of cause of death.

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